Expression of complement and toll-like receptor pathway genes is associated with malaria severity in Mali: a pilot case control study

Malaria Journal

Research

Philippe Leissner¹  Abdoulaye K. Kone²  Amadou Niangaly²  Mahamadou A. Thera²  Abdoulaye A. Djimdé²  Ogobara K. Doumbo²  Antoine Dara³  Scott M. Williams⁴  Jessica E. Manning⁵  Rafal S. Sobota⁶  Christopher V. Plowe⁷  Jason A. Bailey⁷  Guy Vernet⁸ 

[1] BioMerieux, Grenoble, France;Department of Epidemiology of Parasitic Diseases, Malaria Research and Training Center, University of Sciences, Techniques and Technology of Bamako, Bamako, Mali;Department of Epidemiology of Parasitic Diseases, Malaria Research and Training Center, University of Sciences, Techniques and Technology of Bamako, Bamako, Mali;Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, MD, USA;Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA;Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA;Department of Molecular Physiology and Biophysics, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA;Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA;Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, MD, USA;Pasteur Institute of Cameroon, Yaounde, Cameroon, Fondation Merieux, Lyon, France;

关键词: Malaria;    Genetic Epidemiology;    Microarray;    Plasmodium;    Mali;   

DOI  :  10.1186/s12936-016-1189-6

 received in 2015-12-09, accepted in 2016-02-23,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundThe host response to infection by Plasmodium falciparum, the parasite most often responsible for severe malaria, ranges from asymptomatic parasitaemia to death. The clinical trajectory of malaria is influenced by host genetics and parasite load, but the factors determining why some infections produce uncomplicated malaria and some proceed to severe disease remain incompletely understood.MethodsTo identify molecular markers of severe falciparum malaria, human gene expression patterns were compared between children aged 6 months to 5 years with severe and uncomplicated malaria who were enrolled in a case–control study in Bandiagara, Mali. Microarrays were used to obtain expression data on severe cases and uncomplicated controls at the time of acute disease presentation (five uncomplicated and five severe), 1 week after presentation (three uncomplicated and three severe) and treatment initiation, and in the subsequent dry season (late convalescence, four uncomplicated and four severe). This is a pilot study for the first use of microarray technology in Mali.ResultsComplement and toll-like receptor (TLR) pathways were differentially expressed, with severe cases showing higher expression of the C1q, TLR2, TLR4, TLR8, and CR1 genes. Other genes previously associated with malaria pathogenesis, GZMB, FOS and HSPA6, were also higher among severe cases. TLR2, TLR4, TLR8, CR1, GZMB, FOS, and HSPA6 genes were expressed at lower levels in severe cases at late convalescence.ConclusionsOverexpression of genes previously associated with uncomplicated malaria was associated with severe disease. Low baseline expression of these genes may represent candidate markers for severe malaria. Despite the small sample size, results of this pilot study offer promising targets for follow-up analyses.

【 授权许可】

CC BY   
© Sobota et al. 2016